【摘要】：目的:炎癥性腸病(inflammatory bowel disease)是一種慢性非特異的腸道炎癥病變,包括潰瘍性結(jié)腸炎(ulcerative colitis,UC)和克羅恩病(Crohn’s disease,CD)。大量試驗(yàn)研究表明,潰瘍性結(jié)腸炎導(dǎo)致的腸黏膜損傷伴隨著緊密連接結(jié)構(gòu)的破壞,與炎癥黏膜緊密連接蛋白的變化有關(guān),了解潰瘍性結(jié)腸炎腸黏膜屏障功能的改變對(duì)于研究潰瘍性結(jié)腸炎的病因,尋求新的診斷治療方法具有重要意義。方法:將40只Wister雌性大鼠隨機(jī)分為正常對(duì)照組20只,惡唑酮(OXZ)模型組20只,采用7.5mg/ml惡唑酮給模型組大鼠灌腸,模擬潰瘍性結(jié)腸炎模型,等量生理鹽水灌腸做為對(duì)照組,造模后每天觀察大鼠每天飲食、體重變化、大便性狀及潛血情況,評(píng)價(jià)各組大鼠疾病活動(dòng)指數(shù);7天后,采集大鼠血液及結(jié)腸標(biāo)本備檢,觀察并評(píng)價(jià)結(jié)腸黏膜損傷指數(shù)及組織病理學(xué)活動(dòng)指數(shù)分別通過免疫組化和Western blot方法檢測緊密連接蛋白claudin-1,-2,-4及Real-time PCR方法檢測claudin-1,-2,-4 m RNA的表達(dá)情況并用ELISA方法檢測結(jié)腸組織以及血清中細(xì)胞因子TNF-α,IL-4,IL-5,IL-10表達(dá)。結(jié)果:與正常對(duì)照組相比,OXZ模型組大鼠在1~3 d內(nèi)出現(xiàn)大便次數(shù)增多、軟便或稀便、大便末端有黏液或膿點(diǎn),肛周有糞便粘黏等表現(xiàn),少數(shù)有血性腹瀉、毛發(fā)無光澤、體重下降,4只大鼠因癥狀嚴(yán)重而于3d左右死亡;正常對(duì)照組10只大鼠反應(yīng)靈活、飲食量正常、體重增加,均無腹瀉及血便。OXZ導(dǎo)致的潰瘍性結(jié)腸炎大鼠模型組結(jié)腸組織損傷評(píng)分顯著增加(P0.05),結(jié)腸組織以及血清IL-4和IL-5表達(dá)水平顯著升高(P0.05);結(jié)腸組織中claudin-2表達(dá)明顯高于正常對(duì)照組(P0.05),而claudin-1和claudin-4表達(dá)則不同程度低于正常對(duì)照組(P0.05)。結(jié)論:惡唑酮誘導(dǎo)實(shí)驗(yàn)性潰瘍性結(jié)腸炎大鼠緊密連接膜微區(qū)的緊密連接蛋白claudin-1,-2,-4的分布和表達(dá)變化,表明潰瘍性結(jié)腸炎中,緊密連接膜微區(qū)的緊密連接蛋白可能受到了影響,導(dǎo)致腸黏膜屏障功能受損,這一特點(diǎn)可能在潰瘍性結(jié)腸炎中有潛在的診斷治療意義。
[Abstract]:Objective: inflammatory bowel disease (inflammatory bowel disease) is a chronic nonspecific inflammatory disease of the intestine, including ulcerative colitis (ulcerative colitis) and Crohn's disease (CD). A large number of experimental studies have shown that intestinal mucosal damage caused by ulcerative colitis is associated with the destruction of tight junction structure, which is related to the change of inflammatory mucosal tight junction protein. It is important to understand the changes of intestinal mucosal barrier function in ulcerative colitis for studying the etiology of ulcerative colitis and seeking new diagnostic and therapeutic methods. Methods: forty female Wister rats were randomly divided into normal control group (n = 20) and oxazolone (OXZ) model group (n = 20). Rats in the model group were enema with 7.5mg/ml oxazolone to simulate ulcerative colitis. After modeling, the rats were observed daily diet, weight change, stool traits and occult blood. After 7 days of evaluating the disease activity index of rats in each group, blood and colon samples were collected. The colonic mucosal injury index and histopathological activity index were observed and evaluated respectively by immunohistochemical and Western blot methods to detect the expression of claudin-1m-2 RNA in colonic tissues and claudin-1m-2 RNA in colonic tissues detected by Real-time PCR method. The expression of claudin-1m-2 RNA in colonic tissues was detected by ELISA method. The cytokines TNF- 偽, IL-4, IL-5 and IL-10 were expressed in the tissue and serum. Results: compared with the normal control group, the rats in the OXZ model group had increased defecation times, soft or dilute stool, mucus or purulent point at the end of defecation, mucilage around the anus, and a few cases of bloody diarrhea, and the hair had no gloss. Four rats died of severe symptoms in 3 days or so, while 10 rats in the normal control group had a flexible response, normal diet and weight gain. No diarrhea and blood stool. OXZ induced ulcerative colitis model group colonic tissue injury score significantly increased (P0.05), colon tissue and serum IL-4 and IL-5 expression level significantly increased (P0.05), colon tissue claudin-2 expression was significantly higher than normal. The expression of claudin-1 and claudin-4 was lower in the radiation group (P0.05) than that in the normal control group (P0.05). Conclusion: the distribution and expression changes of claudin-1m-2 tip-4 in rat model of experimental ulcerative colitis, indicating that the tight junction protein in the microdomain of tight junction membrane may be affected in ulcerative colitis. This may have potential diagnostic and therapeutic significance in ulcerative colitis.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R574.62

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